ABSTRACT The complications of diabetic foot ulcerations (DFUs) are severe and costly to patients and society. DFUs are quite common: 1 in 4 adults with diabetes will develop a DFU, and 2 out of 3 treated DFUs will recur. Every year, 40,000 individuals lose a leg owing to DFUs. Compared to other groups, Hispanics and Native Americans (NAs) experience a disparate rate of diabetes, foot ulceration, and lower extremity amputation. To date, our understanding of the factors leading to racial and ethnic disparities in major amputations (ankle and above) is limited. Knowledge of the differences in access to care, barriers to limb salvage (amputation prevention), patients' preference in revascularization (improving arterial blood flow for wound healing), and factors related to major amputation are particularly essential to the development of targeted interventions. The goal of this K23 proposal is to address the critical knowledge gap regarding disparities in lower extremity amputations among Hispanics and NAs?vulnerable and often underserved populations. This K23 proposal will leverage the unique and diverse patient populations in the Southwestern Academic Limb Salvage Alliance (SALSA) and the NIH-supported Precision Medicine Initiative Cohort within the All of Us Research Program (AoURP), to determine patient-centered factors that influence the care of the Hispanic and NA populations with DFUs. The objectives of the study include Aim 1: Evaluate the racial and ethnic disparities in healthcare access and utilization among adults with diabetes and DFUs using the cross-sectional survey data of the AoURP; Aim 2: Determine the patient-reported barriers to DFU care and perceived risk factors related to major amputations using focus groups; and Aim 3: Prospectively identify the clinical factors and non-clinical variables (individual, community, and health system-level) related to major amputations among 219 Hispanics and NAs with DFUs. The Classification and Regression Tree (CART) will be used to identify vulnerable subgroups with DFUs that might benefit from early identification and aggressive treatment. The proposed study is significant, as it focuses on the traditionally understudied Hispanic and NA populations. The proposed study is innovative in that it uses the standard Wound, Ischemia, and Foot Infection (WIFi) classification system to stratify the severity of the ulcer presentation. The proposed, rigorous training plan and highly experienced mentorship team composed of national experts in health disparities research, mixed methods research, DFUs and limb salvage, and implementation science will prepare the PI to independently conduct research aimed at designing, conducting, and evaluating culturally competent interventions. Finally, the findings of this study will address a critical knowledge gap regarding disparities in amputations among these vulnerable and underserved groups that continue to make up an increasing portion of the Southwest's population, with the overarching goal of reducing lower extremity amputations among at-risk minority populations.